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The Journal of Immunology, 2003, 170: 6151-6157.
Copyright © 2003 by The American Association of Immunologists

The Autoreactivity of Anti-Phosphorylcholine Antibodies for Atherosclerosis-Associated Neo-Antigens and Apoptotic Cells 1,2

Peter X. Shaw3,*, Carl S. Goodyear{dagger}, Mi-Kyung Chang*, Joseph L. Witztum4,* and Gregg J. Silverman3,4,{dagger}

Divisions of * Endocrinology and Metabolism, and {dagger} Rheumatology, Allergy and Immunology, Department of Medicine, University of California San Diego, La Jolla, CA 92093

Abs specific for phosphorylcholine (PC) are known to contribute to the immune defense against a variety of microbial infections. To assess for other types of binding interactions, we performed surveys of anti-PC Abs of diverse biologic origins and structural diversity and demonstrated a common autoreactivity for oxidatively modified low density lipoprotein and other oxidation-specific structures containing PC-Ags. We also found that cells undergoing apoptosis sequentially express a range of oxidation-specific neo-self PC determinants. Whereas natural Abs to PC recognized cells at early stages of apoptosis, by contrast, an IgG anti-PC Ab, representative of a T cell-dependent response, recognized PC determinants primarily associated with late stages of apoptosis. Cumulatively, these results demonstrate a fundamental paradigm in which Abs from both the innate and the T cell-dependent tiers of the B cell compartment recognize a minimal molecular motif arrayed both on microbes and as neo-self Ags linked to atherosclerosis and autoimmune disease.


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